Metabolic Effects of Switching Kaletra to Boosted Reyataz - Full Text View

Purpose

To study the effects of switching from Kaletra to Boosted Reyataz on glucose, lipids and fat in HIV-infected patients.

Condition	Intervention
HIV Infections	Drug: atazanavir/ritonavir Drug: lopinavir/ritonavir


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Metabolic Effects of Switching Kaletra to Boosted Reyataz

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Lopinavir Atazanavir Atazanavir sulfate

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Glucose Trafficking [ Time Frame: 6 months ] [ Designated as safety issue: No ]
6 month mean and standard deviation for glucose uptake into anterior thigh muscle as measured by FDG/PET scanning during euglycemic hyperinsulinemic clamp. During the hyperinsulinemic conditions of the clamp, glucose and 18-FDG [labeled glucose] are taken up by muscle. The quantity of 18-FDG taken up is measured by the PET scan. Although there are no well-accepted norms for this measurement, a higher value indicates that more glucose is being taken up by (or "trafficked to") muscle. Increased uptake of glucose indicates increased muscle insulin sensitivity.

Secondary Outcome Measures:

Insulin Sensitivity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
6 month mean and standard deviation for insulin-stimulated glucose uptake (M) per unit insulin at 120 minutes as measured by euglycemic hyperinsulinemic clamp.
Fasting Glucose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
6 month mean and standard deviation for fasting glucose.
Lipid Metabolism - Serum Triglyceride [ Time Frame: 6 months ] [ Designated as safety issue: No ]
6 month mean and standard deviation for serum triglyceride.
Body Composition - Visceral Adipose Tissue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
6 month mean and standard deviation for visceral adipose tissue (VAT) as measured by single slice computed tomography (CT) scan at the L4 pedicle (pedicle of 4th lumbar vertebra).
Immune Parameters -- CD4 Count [ Time Frame: 6 months ] [ Designated as safety issue: No ]
6 month mean and standard deviation for CD4+ count.
Liver Enzymes -- Aspartate Aminotransferase (AST) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
6 month mean and standard deviation for AST.
Liver Enzymes -- Alanine Aminotransferase (ALT) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
6 month mean and standard deviation for ALT.
Total Bilirubin [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
6 month mean and standard deviation for total bilirubin.


Enrollment:	15
Study Start Date:	May 2006
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Boosted Reyataz (300mg atazanavir + 100mg ritonavir)	Drug: atazanavir/ritonavir atazanavir 300mg + ritonavir 100mg once daily Other Name: Boosted Reyataz
Active Comparator: 2 Kaletra (pre-study dose)	Drug: lopinavir/ritonavir patient remains on their pre-study dose of lopinavir/ritonavir Other Name: Kaletra

Detailed Description:

The primary objective of this study is to determine tissue specific glucose trafficking in patients before and after switching from a regimen containing Lopinavir/ritonavir (LPV/r) to one containing atazanavir/ritonavir (ATV/r). Secondary outcome measures of interest will include insulin sensitivity determined by clamp testing, and lipid metabolism and hepatic glucose production assessed using stable isotope techniques. We hypothesize that switching protease inhibitor (PI) to ATV/r from LPV/r will result in direct increases in glucose uptake in muscle and visceral adipose tissue in association with improvements in overall whole body insulin sensitivity compared to remaining on LPV/r. We will complete a prospective randomized trial of Human Immunodeficiency Virus (HIV) infected patients who have been on a stable antiretroviral (ARV) regimen containing LPV/r for at least 6 months and who will be randomized to either switch to a regimen containing ATV/r or remain on LPV/r for 6 months. Each subject will complete Positron Emission Tomography (PET) 18-fluorodeoxyglucose (FDG) imaging during a hyperinsulinemic clamp study at baseline and 6 months after randomization.

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Previously diagnosed HIV infection
Age between 18-65 years
Stable antiviral regimen containing at least 2 nucleoside reverse transcriptase inhibitors (NRTI's) and LPV/r for ³ 6 mos
CD4 count > 400 cell/mm3
Metabolic complication as indicated by one or more of hyperinsulinemia (fasting insulin >= 15 mIU/ml), hypercholesteremia (fasting total cholesterol >= 200 mg/dL), hypertriglyceridemia (fasting triglycerides >= 150 mg/dL), or treatment with a lipid lowering medication.

Exclusion Criteria:

Hemoglobin < 11.0 g/dL
History of Diabetes Mellitus
Currently on medication for Diabetes
Therapy with glucocorticoid, growth hormone or other anabolic agents currently or within the past 3 months
Current substance abuse, including alcohol, cocaine and/or heroin
Any contraindication to ATV/r or known allergy to ATV
Concurrent therapy with: Bepridil; cisapride; ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine); indinavir; irinotecan; lovastatin; midazolam; pimozide; proton pump inhibitors (esomeprazole, lansoprazole, omeprazole); rifampin; simvastatin; St John's wort; or triazolam
New or serious opportunistic infection in the past 3 months
Pregnancy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413153

Locations


United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Bristol-Myers Squibb

Investigators


Principal Investigator:	Steven K Grinspoon, MD	MGH

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stanley TL, Joy T, Hadigan CM, Liebau JG, Makimura H, Chen CY, Thomas BJ, Weise SB, Robbins GK, Grinspoon SK. Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on muscle glucose uptake and visceral fat in HIV-infected patients. AIDS. 2009 Jul 17;23(11):1349-57. doi: 10.1097/QAD.0b013e32832ba904.


Responsible Party:	Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00413153 History of Changes
Other Study ID Numbers:	2005-P-002239
Study First Received:	December 15, 2006
Results First Received:	November 4, 2009
Last Updated:	March 5, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:


HIV Kaletra Reyataz Insulin sensitivity	Lipids Body Composition Receiving Kaletra Treatment Experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Lopinavir Ritonavir	Atazanavir Sulfate HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016